Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

Human T-cell lymphotropic virus type 1 (HTLV-1) induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females) was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males). Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1). There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06) and IL-5 levels were higher (P = 0.02) in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004) in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

Multiclonal Leishmania braziliensis population structure and its clinical implication in a region of endemicity for American tegumentary leishmaniasis.

In Corte de Pedra (CP), northeastern Brazil, Leishmania braziliensis causes three distinct forms of American tegumentary leishmaniasis (ATL). To test the hypothesis that strain polymorphism may be involved in this disease spectrum and accurately characterize the parasite population structure in CP, we compared one L. major, two non-CP L. braziliensis, one CP L. amazonensis, and 45 CP L. braziliensis isolates, obtained over a 10-year period from localized cutaneous, mucosal, and disseminated leishmaniasis patients, with randomly amplified polymorphic DNA (RAPD). Electrophoretic profiles were mostly unique across species. All typing protocols revealed polymorphism among the 45 CP L. braziliensis isolates, which displayed eight different RAPD patterns and greater than 80% overall fingerprint identity, attesting to the adequacy of the tools to assess strain variability in CP's geographically limited population of parasites. The dendrogram based on the sum of RAPD profiles of each isolate unveiled nine discrete typing units clustered into five clades. Global positioning showed extensive overlap of these clades in CP, precluding geographic sequestration as the mechanism of the observed structuralization. Finally, all forms of ATL presented a statistically significant difference in their frequencies among the clades, suggesting that L. braziliensis genotypes may be accompanied by specific disease manifestation after infection.

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

Mucosal leishmaniasis is characterized by an intense inflammatory reaction and tissue damage with few parasites in the lesion. On the basis of previous observations that suggest a possible role of tumor necrosis factor alpha (TNF-alpha) in the pathology of this disease, an open-label study was performed to evaluate the efficacy of the treatment with an inhibitor of TNF-alpha (pentoxifylline) associated to antimony therapy in 10 patients with refractory mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3 times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure: they experienced complete reepithelization of the mucosal tissue 90 days after therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF-alpha levels before therapy (776 +/- 342 pg/mL) fell to 94 +/- 57 pg/mL (P < 0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus antimony therapy should be considered in all patients with mucosal leishmaniasis that is refractory to treatment.

Mucosal leishmaniasis: quantitative nasal cytology as a marker of disease activity and indicator of healing.

Mucosal leishmaniasis (ML) follow-up is based on subjective parameters. Using simplified quantitative cytology of nasal lavages (QNCs), we studied 20 ML patients, 10 patients with cutaneous leishmaniasis (CL), and 10 healthy subjects. Patients with ML were treated with antimony and followed up with otolaryngological examination plus QNCs for 6 months. At the first evaluation, the median total number of cells in ML patients (1,540,000) was greater than that in CL patients (215,000) or that in healthy subjects (250,000). Neutrophils were predominant in ML patients, in contrast to both sets of controls, in whom epithelial cells were more frequent. During treatment, we found a significant reduction in total nasal cell counts in ML patients who were cured, and encountered a switch in predominant cell type. The cytology of 2 patients who did not respond to antimony remained the same. It is therefore possible to detect nasal inflammation in ML patients through QNCs, which may indicate extension of mucosal involvement, providing an objective parameter to monitor therapy.

[Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up]. / Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento.

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento / Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Em 1996 foram avaliados clinicamente 20 dos 21 pacientes com leishmaniose mucosa, tratados em 1994 com sulfato de aminosidine 16mg do sal/kg/dia, intramuscular, por 20 dias. Um paciente foi a óbito por causas não relacionadas com a leishmaniose mucosa. Dos 14 pacientes (66,7% N = 21) que inicialmente alcançaram a remissão completa dos sinais e sintomas durante os três primeiros meses de seguimento, sete (50% N = 14) permaneceram livres de doença por 24 meses e sete pacientes apresentaram recidiva neste período. O acompanhamento sorológico mostrou pobre correlação com a avaliação clínica.

Clinical observations of unresponsive mucosal leishmaniasis.

We report the long-term clinical follow-up of two patients with unresponsive mucosal leishmaniasis due to Leishmania (Viannia) braziliensis from the Três Braços area in Bahia State, Brazil. Both were agricultural male workers with extensive upper respiratory mucosal involvement that was not cured with conventional and experimental therapy.

[Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis]. / Estudo terapêutico aberto com sulfato de aminosidine na leishmaniose mucosa causada por Leishmania (Viannia) braziliensis.

From September to November 1994. 21 patients with active mucosal leishmaniasis were treated with aminosidine sulphate 16 mg/kg/day by intramuscular injection for 20 days. They were principally adult male agricultural workers. Thirteen patients had not received specific treatment and eight had failed to respond to Glucantime therapy. Diagnosis was based on clinical and epidemiological observations, a search for the parasite, leishmanin skin sensitivity and indirect fluorescent antibody serological tests. Sixty seven percent of patients had leishmania parasites isolated from inoculated hamsters or visualized in imprints or histopathological sections. The mean follow-up period was 12.6 months. All patients completed treatment. Side effects were pain at the injection site (86%); mild proteinuria (24%), elevated serum creatinine (.5%) and subclinical bearing loss in one of two patients who did audiometric tests. Clinical cure was achieved in 48% and the accumulated relapse rate was 29% (4/14).